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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Gauster, M; Oskolkova, OV; Innerlohinger, J; Glatter, O; Knipping, G; Frank, S.
Endothelial lipase-modified high-density lipoprotein exhibits diminished ability to mediate SR-BI (scavenger receptor B type I)-dependent free-cholesterol efflux.
Biochem J. 2004; 382(Pt 1):75-82 Doi: 10.1042/BJ20031882 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Frank Sasa
Gauster Martin
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Abstract:
Endothelial lipase (EL) is a phospholipase with little triacylglycerol lipase activity. To assess structural and functional properties of EL-HDL (EL-modified high-density lipoprotein), HDL was incubated with conditioned medium from Cos-7 cells infected with adenovirus encoding human EL. After re-isolation of HDL by ultracentrifugation, TLC and HPLC analyses revealed that EL-HDL was markedly depleted in phosphatidylcholine and enriched in lyso-phosphatidylcholine compared with LacZ-HDL (control HDL) incubated with conditioned medium from Cos-7 cells infected with adenovirus encoding beta-galactosidase. The EL-HDL was enriched in non-esterified fatty acids and, as revealed by lipid electrophoresis, was more negatively charged than control HDL. The HDL particle size as well as the total cholesterol, free cholesterol and triacylglycerol content of HDL were not significantly altered after EL modification. The ability of EL-HDL to mediate 3H-cholesterol efflux from SR-BI (scavenger receptor B type I) overexpressing Chinese-hamster ovary cells was impaired and markedly lower compared with LacZ-HDL at HDL concentrations of 100 microg/ml and above. Studies with 125I-labelled HDL showed almost unaltered binding affinity (K(m) values) and a slightly but significantly decreased binding capacity (B(max) values) of EL-HDL to SR-BI, compared with LacZ-HDL. The ATP-binding-cassette transporter A1-dependent cholesterol and phospholipid effluxes were not affected by EL modification. From these results, we concluded that EL modification alters chemical composition and physical properties of HDL, resulting in its decreased binding capacity to SR-BI and a diminished ability to mediate SR-BI-dependent cholesterol efflux.
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Find related publications in this database (Keywords)
adenoviral vector
cholesterol efflux
phospholipase
reverse cholesterol transport
scavenger receptor B type I (SR-BI)
structure-function
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